1. Field of the Invention
Wounds resulting from cuts, abrasions, burns, skin ulcers, skin grafts, and the like can affect large areas of the skin and require lengthy periods to heal. Long healing times are a particular problem with wounds on sensitive areas, such as corneal wounds, which are difficult to treat over prolonged periods. For these reasons, there has been a long-felt need for a pharmacological agent which will promote rapid healing of skin and corneal wounds.
Heretofore, a number of research groups have investigated the use of epidermal growth factor obtained from mouse salivary glands (mEGF) to promote the regeneration of epidermal wounds. Thus far, the treatment of relatively large wounds resulting from abrasions, burns, and the like with mEGF has proved to be of only marginal value in promoting wound healing. Although the use of mEGF in promoting healing of corneal epithelial wounds has been more promising, such treatment has not been shown to be effective in accelerating the rate of healing of corneal stromal wounds.
It would thus be desirable to provide a method and agent for treating epithelial, stromal and corneal wounds which will promote the rapid healing of these wounds. In particular, it would be desirable to provide such an agent in large quantities and in formulations which are suitable for treatment of the affected area.
2. Description of the Prior Art
A comparison of human and mouse epidermal growth factor (EGF) and a discussion of their activities in vivo and in vitro are presented in Hollenberg, "Epidermal Growth Factor-Urogastrone, a Polypeptide Acquiring Hormonal Status", Academic Press, Inc., New York (1979), pp. 69-110. See also Carpenter, "Epidermal Growth Factor" in Handbook of Experimental Pharmacology, Vol. 57, Baserga, ed., Springer Verlag, Berlin (1981), pp. 90-132; and Carpenter (1979) Ann. Rev. Biochem. 48: 193-216.
Various studies have examined the use of mEGF in treating epidermal wounds. Greaves (1980) Clin. Exp. Dermatol. 5: 101-103, applied mEGF on blister wounds on human subjects. The mEGF in saline solution was applied once daily until the wounds healed. No acceleration in the growth of the epidermal layer was observed. Topical application of mEGF to open wounds in mice has been found to promote healing in various degrees. See, e.g., Niall et al. (1982) J. Surg. Res. 33: 164-169; Thornton et al. (1981) Burns 8: 156-160.
The use of mEGF to promote the healing of corneal epithelial wounds has been described. See, e.g., Daniele et al. (1979) Graefes Archives Opththalmologie 210: 159-165; Ho et al. (1974) Invest. Ophthalmol. 13: 804-809; Elliott (1980) Trans. Amer. Ophthalmol. Soc. 30: 629-656; and Gospodarowicz et al. (1977) Exp. Eye Res. 25: 75-89.